Population dynamics of “null” and Thy1 lo lymphocytes in mouse bone marrow: Genesis of cells with natural killer cell lineage characteristics

Abstract

The population dynamics of “null” small lymphocytes lacking B and T lineage markers in mouse bone marrow have been examined using a combination of immunolabeling and hydroxyurea (HU) deletion techniques. The binding of the B lineage-associated mAb, 14.8, and anti-Thy1.2 to bone marrow cells has been detected radioautographically. Null cells lacking 14.8 and Thy 1.2 determinants (14.8 − ThyI −) formed a substantial subset (12–14%) of bone marrow small lymphocytes, representing 0.5 × 10 6 cells per femur (2–3% of nucleated cells). HU treatment revealed an exceptionally rapid turnover of the null small lymphocyte population ( T 1 2 , 7.5 hr) compared with 14.8 + cells ( T 1 2 , 20.5 hr) and Thy1 + cells ( T 1 2 , 53 hr). Small lymphocytes bearing low intensities of Thy1 (Thy1 lo) were also rapidly renewed ( T 1 2 , 28 hr) whereas those with high intensities of Thy1 (Thy1 hi) were renewed only slowly ( T 1 2 , 123 hr). During ontogeny, null small lymphocytes first appeared in the fetal liver by Day l 1 and the fetal spleen by Day 16, but increased rapidly in the bone marrow in early postnatal life. Double immunolabeling techniques demonstrated that 10% of null small lymphocytes in the bone marrow expressed NK1.1 antigen, while larger proportions bound to tumor (YAC.1) cells in vitro and displayed Fc receptors. The NK1.1-bearing fraction of null small lymphocytes in bone marrow was depleted by HU treatment only after an initial delay. NK1.1 was also expressed on subsets of Thy1 lo cells and Thy1 hi cells. The results have revealed the continuous production in mouse bone marrow of null and Thy 1 lo small lymphocytes, totaling 1−3 × 10 7 cells/day and 1.2 × 10 6 cells/day, respectively. The findings suggest that the large-scale production of null lymphocytes in mouse bone marrow includes the genesis of NK lineage cells which express NK1.1 and Thy1 lo during a period of terminal maturation.